DESCRIPTION: (Adapted from applicant's description) This research is based on the hypothesis that, in gonadotropes, a cellular protein, FKBP12 may be a regulatory protein for IP3 receptors and be controlled via GnRH signaling. The broad goal of the proposal is to evaluate the role of FKBP12 in the regulation of IP3 Receptor function and GnRH-induced LH secretion. The study proposes to quantify the contribution of FKBP12 to GnRH-induced LH secretion using in vitro and in vivo models and to determine whether expression, assembly, or phosphorylation of the IP3-Receptor complex is regulated by hormones that alter sensitivity to GnRH. The projects should provide information about the GnRH stimulated PKC pathway leading to calcium release from the endoplasmic reticulum. It will use a drug, FK506, to test the role of FKBP12. FK506 is an immunosuppressive drug that is widely used in organ transplants. Thus, information about its potential role in the reproductive system would also be obtained.